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Symposium on Therapy: Complications and Management October 1964 Volume 3, Number 5 INVESTIGATIVE OPHTHALMOLOGY Symposium on therapy: Complications and management Cardiovascular renal agents as they impinge on ophthalmic practice John E. Harris I t is the purpose or this review to discuss that this does not produce additive effects the effects of cardiovascular renal agents as which may be toxic. they may relate to ophthalmic practice. While the drugs in general are grouped Antihypertensive agents according to their major therapeutic use, The past decade and a half has seen the I should like to emphasize within this synthesis of many antiarterial hypertensive framework, first, those which are used by agents as well as the isolation of the active the ophthalmologist in the treatment of principles of certain natural products. ocular disease; second, those which may Table I by no means lists all the agents have an effect on the eye, but which are which have been developed, nor is the not primarily used in the treatment of classification necessarily descriptive of the ocular disease; and, third, the toxicity which mode of action of the drug. Particularly may result from either the systemic use this is true of the first and third groupings. of agents employed for ocular conditions Under the first classification, that of or the combination of these with cardio- drugs acting at or near peripheral nerve vascular renal drugs which the patient is endings, we are dealing with a variety of taking for other reasons. Particularly the agents which have quite different modes latter deserves mention. Often the patient of action. I have included, for its historic presents with multiple vials of pills he is interest, Dibenamine, an example of adren- taking. It is the responsibility of the oph- ergic blocking agents, which, incidentally, thalmologist who may place this patient are no longer in favor in the treatment of on some systemic medication to be certain hypertension. Dibenamine was the first of its type made available for study, and second it was the first of the systemic From the Department of Ophthalmology, Univer- agents, excluding the osmotic agents, which sity of Minnesota Medical School, Minneapolis, enjoyed at least some temporary success Minn. in the treatment of glaucoma. Christensen 481 Downloaded from iovs.arvojournals.org on 10/01/2021 482 Harris Investigative Ophthalmology October 1964 Table I. Some antihypertensive agents in There are newer drugs which exert a current use peripheral effect somewhat similar to that of the Rauwolfia derivatives. Among these I. Act at peripheral nerve endings Dibenamine (not in use) are guanethidine (Ismelin) and bretylium Guanethidine (Ismelin) tosylate (Darenthin). These drugs affect Bretylium tosylate (Darenthin) only the sympathetic nervous system and Reserpine have been found to be of value in the Alpha methyldopa (Aldomet) Pargyline HC1 (Eutonyl) treatment of hypertension. They produce a similar clinical effect, although their II. Ganglion blocking agents modes of action may differ. Thus guanethi- Tetraethylammonium chloride (Etamon) Hexamethonium chloride (Bistrium) dine is a norepinephrine depleter whereas Pentolinium tartrate (Ansolysen) bretylium tosylate is not. Of these, guan- Mecamylamine (Inversine) ethidine is of particular interest since it has 111. Others been shown to lower the intraocular pres- Hydralazine (Apresoline) sure. While it reduces the norepinephrine Reserpine at the nerve endings and blocks the effect Veratrum preparations of nerve stimulation, it does not block the action of injected norepinephrine or epi- nephrine. Indeed, the pressor effect of these and Swan first reported the value of this agents is actually greater in the animal pre- drug as an ocular hypotensive agent. treated with guanethidine. In this respect Others corroborated this report. The agent the action of the drug simulates a surgical (no longer available) had to be admin- sympathectomy. istered intravenously and this made its use Guanethidine has been shown to pro- limited. Nonetheless, it proved of value in duce a delayed miosis and drop in ocular certain cases of acute glaucoma which did tension in the rabbit. Our own experience not respond to standard treatment. The in the laboratory indicated that the drug mode of action of this agent is not certain had no effect on the intraocular pressure but it appears to reduce the rate of aqueous of the normal cat when administered topi- formation. cally or injected into the internal maxillary The Rauwolfia alkaloids occupy an in- artery. It did produce a drop in the in- teresting position among the antihyperten- traocular pressure when injected into the sive agents. Of these perhaps the most femoral vein but this paralleled the fall in widely used is reserpine. It is among the the arterial blood pressure and presum- group of antihypertensives that is known ably was caused by it. However, ours were to deplete the body stores of norepineph- acute experiments. In humans, adminis- rine. Because it produces alterations of tered topically either alone or as an adju- mood and behavior, it originally was vant, it does lower the intraocular pressure thought to exert its arterial hypotensive in glaucomatous eyes. We were originally action via the central nervous system. The quite enthusiastic, but now feel that it view is logical since reserpine is known to offers little improvement over standard reduce the central nervous system stores forms of topical therapy. There would ap- of norepinephrine. The drug has also been pear to be no contraindications to the found to deplete peripheral stores of nor- combined uses of any of these agents and epinephrine and therein may hinge its the systemic agents which the ophthalmol- mechanism of action as an antihyperten- ogists might employ. sive. Of the drugs which the ophthalmol- The enzyme inhibitors present an in- ogists may use systemically, there is none teresting group of antiarterial hyperten- which could not be readily combined with sives. One group consists of the decarboxy- the Rauwolfia derivatives. lase inhibitors of which the principal one Downloaded from iovs.arvojournals.org on 10/01/2021 Volume 3 Cardiovascular renal agents 483 Number 5 is alpha methyldopa (Aldomet). It blocks ness have resulted from a too profound the decarboxylation of aromatic amino depression of the systemic blood pressure acids and consequently reduces the pro- by these drugs, usually at surgery. Their duction of catecholamines, including nor- mixture with agents that ophthalmologists epinephrine and serotonin. In spite of the might use should produce no harmful ad- good biochemical data and inferences, the ditive effects. exact mechanism by which this enzyme in- The other drugs have varied sites of ac- hibitor influences hypertension is not tion. The effect of hydralazine, once known. Alpha methyldopa has been tested thought to be central, is now considered to for possible ocular hypotensive action with be directly on the smooth muscle of the both topical and systemic routes of ad- arterioles. The effect of the veratrum deriv- ministration and has been found to have atives has been shown to be on the baro- little or no effect. There would appear to ceptors and chemoceptors of the carotid be no contraindication to the combined use sinus, the aortic arch, etc. These drugs of this agent and those which an ophthal- have no use in the treatment of ocular mologist might employ. disorders, although presumably they would An even more interesting example of en- lower the intraocular pressure by virtue zyme inhibition of arterial hypertension is of their effect on the blood pressure. There that of the inhibitors of monoamine oxi- is no contraindication to their use in the dase. The enzyme itself sometimes has been treatment of ophthalmic disorders. regarded as the one responsible for the Before leaving the antihypertensive in activation of epinephrine and norepi- agents, I would like to consider the ques- nephrine. This does not seem to be the tion of arterial hypertensive crises which case. The inhibitors of this enzyme, of the ophthalmologist may encounter. Very which pargyline HC1 (Eutonyl) is an ex- rarely is it necessary for the ophthalmolo- ample, cause postural hypotension. They gist to treat these conditions, but, occasion- seem to exert their effect by preventing ally, particularly postsurgically, a hyper- the release of norepinephrine at sympa- tensive crisis may result that requires treat- thetic nerve endings in a manner which is ment. There is a variety of agents that not understood and, indeed, may not even might be used for this purpose. These be related to the inhibition of the enzyme. have largely been covered by Gifford. We The ganglion blocking agents have been have preferred reserpine, giving it general- fairly extensively employed. They are po- ly intravenously although intramuscular in- tent hypotensive agents. These drugs block jection is probably just as adequate. Re- both parasympathetic and sympathetic serpine does not reduce the blood pressure ganglia and thus have the unwanted side as rapidly as many of the other agents. effect of blocking the parasympathetic ner- Thus, readministration of this drug, if a vous system. This would appear to accoimt more profound effect is desired, should be for one of the undesirable side effects of delayed for one to two hours, lest the pa- these agents, i.e., blurring of vision, an tient suffer too great a drop in blood pres- effect, incidentally, which is reported to be sure. blocked by pilocarpine. They have been Perhaps a more commonly encountered reported to lower the intraocular pressure. condition is the hypotensive crisis. This Presumably this is due to the drop in blood usually presents to the ophthalmologist pressure but this cannot be stated with cer- when the patient arrives at the operating tainty. Their use for this purpose would room and may be the result of the pre- certainly be infrequent. The only instance operative medications. The usual support- might be in an acute glaucomatous eye ive therapy is indicated of course.
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